Behavioral and biological research on drug abuse will be conducted in multidisciplinary inpatient clinical studies of heroin addicts and polydrug users. behavioral studies of narcotics abuse propose to evaluate three new pharmacotherapies: (1) Buprenorphine, a new partial agonist-antagonist; (2) Non-narcotic polypeptide and steroid hormones with no known addiction liability; and (3) Naltrexone, a long acting antagonist drug. The effects of these compounds on heroin self-administration and its subjective and objective consequences will be examined in double-blind controlled studies. Biological studies of narcotics abuse include: (1) examination of the effects of heroin and buprenorphine on pituitary-gonadal hormones; (2) study of covariance of opiate induced chages in mood states with hormone levels; (3) assessment of tolerance to heroin induced alt rations in testosterone, luteinizing hormone (LM) and prolactin (PRL); (4) correlation of hormonal tolerance with behavioral and physiologcal indices of opiate tolerance. Behavioral studies of polydrug use propose to examine: (1) the effects of concurrent availability of marihuana and alcohol on patterns of durg acquisition and use; (2) subjective consequences of concurrent alcohol plus marihuana use, as contrasted to single drug use; (3) the effects of concurrent use of heroin, alcohol and marihuana on cigarette smoking. Behavioral and pharmacological factors which influence polydrug use patterns will be explored. Findings from the proposed clinical studies should contribute to improved durug abuse treatemnt and prevention strategies, as well as to a better understanding of the behavioral and biological effects of drugs and how these influence the maintenance of drug self-administration in man.